Eli Lilly's $8 billion buyout of biotech Loxo Oncology was the largest acquisition in the Indianapolis-based pharma's 143-year history. New study results for a cancer therapy acquired in that deal suggest Loxo was worth the price.
While Loxo has already won U.S. approval for one drug, called Vitrakvi and now owned by Bayer, Lilly's interest in Loxo centered on a targeted treatment for tumors with uncommon abnormalities in a gene known as RET.
Updated data for that drug, announced Monday at the World Conference on Lung Cancer, are striking. Among 105 patients with RET fusion-positive non-small cell lung cancer, 68% saw their tumors shrink following treatment with LOXO-292, as the therapy's called. Two percent were complete responses, while 66% were partial.
Early analysis, which could change, calculated the median length of response at just over 20 months, and the time until disease progression at 18 months — substantially higher than what some analysts on Wall Street were predicting. As few progression events have occurred, neither number is yet considered statistically stable.
The findings are also notable because LOXO-292 was mainly tested in patients whose cancers had evaded prior therapies. More than half were previously treated with immunotherapies like Merck & Co.'s Keytruda, and all had received platinum-based chemotherapy before.
Among an additional 34 new-to-treatment study participants, 85% responded to LOXO-292.
LOXO-292 also appeared to be well-tolerated. Only nine patients among the 531 enrolled in Lilly's study of the drug discontinued treatment due to treatment-related toxicity.
For Lilly, the data validates why the company moved quickly to acquire Loxo after seeing initial results from LOXO-292 last summer and fall.
"It was a bet on the data, but it wasn't a super risky bet on the data," said Dan Skovronsky, Lilly's chief scientific officer, in an interview.
Lilly plans to file for U.S. approval of LOXO-292, also called selpercatinib, in both RET-altered lung and thyroid cancers by the end of this year. The company plans to present updated thyroid data at the European Society of Medical Oncology's annual meeting later this month.
Targeted therapy advances
Alterations in the RET gene occur in an estimated 2% of lung cancers and between 10% and 20% of thyroid cancers. Loxo estimates put the number of patients eligible for late-line treatment at about 5,000 per year in the U.S.
To date, no drug specifically targeting RET has been approved, so doctors usually turn to chemo, immunotherapy, or a less-specific type of targeted treatment. Response rates to the latter are modest, at about 30%, while studies suggest drugs like Keytruda are less efficacious in lung cancers spurred by a "driver" genetic alteration like RET.
Speaking to BioPharma Dive, Lilly and Loxo executives were optimistic LOXO-292 could play a similar role in treating RET-positive lung cancers as AstraZeneca's Tagrisso and Roche's Alecensa have for EGFR- and ALK-mutated tumors, respectively. All three drugs work by targeting proteins known as kinases.
"It's a little apples and oranges admittedly, but osimertinib and alectininb in their equivalent second- or third-line populations have median progression-free survival of nine to 10 months," said Jacob Van Naarden, chief operating officer at Loxo, referring in an interview to Tagrisso and Alecensa by their nonproprietary names.
"We're in good company here."
Lilly will have competition, however. Blueprint Medicines is developing a rival therapy for RET-driven cancers, and in June presented data showing about 60% of 48 lung cancer patients responded to treatment with its drug.
The bar is raised, too, as Tagrisso, Alecensa and other kinase inhibitors have changed what's considered strong results.
"Our expectations are high for new targeted therapies," said Alice Shaw, director of thoracic oncology at Massachusetts General Hospital in Boston, in an email. Shaw has consulted with both Loxo and Blueprint, and has used both drugs to treat patients with RET-positive patients.
For the first-line setting, "a median PFS exceeding 12 months would be very notable, and exceeding 24 months would be exceptional," she added.
Lilly hopes LOXO-292 could eventually become a first-line treatment for RET cancers, and is planning a Phase 3 study comparing the drug against Keytruda plus chemotherapy — a now standard combination — in treatment-naive non-small cell lung cancer.
Turning a corner?
At $8 billion, Lilly's acquisition of Loxo easily surpassed a 2008 deal for ImClone Systems as the company's largest. That buy, like the one of Loxo, centered on a cancer drug and was pitched as a path for the pharma to become a "true oncology powerhouse."
While ImClone gave Lilly Erbitux and Cyramza, the company's broader ambitions in the field never fully panned out, and it's missed out on the recent immuno-oncology boom.
Buying Loxo, along with an earlier $1.6 billion takeover of Armo BioSciences, are part of the company's effort to revitalize its cancer business, a push that's also involved several high-profile hires from academia.
Results so far are mixed. While Lilly's breast cancer drug Verzenio has some momentum, the company in April pulled its sarcoma therapy Lartruvo from the market after negative findings in a Phase 3 study. Last quarter, the company earned just under $1.2 billion from its cancer drugs, up about 8% from the same period in 2018.
Lilly officials, though, describe the company as having turned a corner.
"Lilly Oncology is in the best place that it's been in for probably over a decade, certainly as long as I've been observing it," said Skovronsky, who joined Lilly in 2010.
"We're finally making progress in three key areas," he added, ticking off commercial performance, data readouts for existing drugs like Verzenio and Cyramza, and the deals for Loxo and Armo.
The addition of Loxo could have a more pronounced impact on Lilly's oncology future than just LOXO-292. In August, Lilly named Loxo CEO Josh Bilenker as its interim head of cancer research and early stage drug development, replacing the outgoing Levi Garraway.
"We can improve and learn from some of the great things that Loxo has been able to do," said Skovronsky.